1. Field of the Invention
Embodiments of this invention are directed generally to biology, medicine, and immunology. Certain aspects are directed to immunogenic fibrils and their use in inducing an immune response.
2. Description of Related Art
Polypeptides that non-covalently assemble into supramolecular structures, such as nanofibers and nanoparticles, are receiving increased interest as biomaterials for diverse applications, including enzyme catalysis (Wheeldon 2009; Baxa 2002; Patterson 2012; Guglielmi 2009) biosensors (Leng 2010; Men 2009), electronics (Baldwin 2006; Wheeldon 2008), tissue engineering (Wang 2011; Horii 2007), drugs and drug delivery (Webber 2012; Matson 2011; Sinthuvanich 2012), and immunotherapy (Rudra 2010; Hudalla 2013; Black 2012; Wahome 2012). In part, this widespread applicability arises from the ability to incorporate a self-assembling domain and a bioactive ligand, such as a peptide, protein, or nucleic acid, into a single molecule via recombinant genetic fusion or chemical synthesis approaches, without perturbing the assembly or bioactive properties of the respective domains (Cardinale 2012; Lim 2009; Woolfson 2010; Guler 2005). In addition, mixtures of self-assembling polypeptides with or without appended bioactive ligands co-assemble into multi-component biomaterials, in which molecular composition is governed by the molar ratio of polypeptides present during assembly (Collier 2008; Collier 2010; Matson 2012; Minten 2009; Minten 2011). Importantly, this precise and reproducible compositional control enables use of statistical methods to identify ligand formulations that elicit optimal functional responses (Jung 2011), which can be challenging to achieve with co-polymer blends that are subject to compositional drift. However, supramolecular assemblies bearing multiple different folded protein ligands at precise concentrations have not yet been realized, despite existing approaches to create assemblies having tunable concentration of a single protein ligand (Hudalla 2013; Minten 2009; Sangiambut 2013), or bearing two different biologically active proteins (Leng 2010; Men 2009; Minten 2011). A general approach that enables modular and tunable control over integrated protein ligand composition would provide enormous nanofiber design flexibility, ultimately leading to new biomaterials with unique biological or chemical properties for various downstream applications.